Urvant L. Localization of the sites in coiled-coil connector of fibrin molecule which are involved in the protofibrils lateral association

It was shown that exposition of the Bbeta121-138 site is not associated with removing of alphaC-regions from the bulk of the molecule during fibrin polymerization. It was established that the exposition of the Bbeta121-138 site in coiled-coil connector occurs at fibrinogen to fibrin transformation as a result of the cleavage of fibrynopeptides A by thrombin and the formation of fibrin desA monomer. It was first shown the changes of the alpha-helix conformation of the Bbeta121-138 site during fibrinogen to fibrin transformation. This structural rearrangement is that the inflected Bbeta121-138 site is straightened and exposed towards the solvent due to the changes of the interactions between amino acid residues in pairs of alpha-beta, alpha-gamma and beta-gamma chains. Blocking of the fibrin Aalpha20-78 region by monoclonal antibody II-5c inhibits the exposition of Bbeta121-138 site. This fact allowed us to suggest that the interaction of fibrinogen with thrombin apolar site and cleavage of the fibrynopeptides A leads to the exposition of the Bbeta121-138 site. The site involved in the lateral association of fibrin protofibryls was localized more exactly in the Bbeta126-135 locus belonging the hinge zone of fibrin molecule. It has been found that the other constituent of the hinge zone of fibrin molecules gamma69-77 is also involved in the fibrin protofibryls lateral association. These data suggest that during fibrinogen to fibrin conversion in the hinge zone of coiled-coil connector Aalpha91-103, Bbeta126-135, and gamma69-77 the new fibrin structure is formed which is necessary for the process of protofibryl lateral association. This part of fibrin coiled-coil is considered as the site that is involved in this process.